Analytical characterization and pharmacological evaluation of the new psychoactive substance 4‐fluoromethylphenidate (4F‐MPH) and differentiation between the (±)‐threo and (±)‐erythro diastereomers

Abstract

Misuse of (±)-threo-methylphenidate (methyl-2-phenyl-2-(piperidin-2-yl)acetate; Ritalin®; MPH) has long been acknowledged, but the appearance of MPH analogs in the form of 'research chemicals' has only emerged in more recent years. 4-Fluoromethylphenidate (4F-MPH) is one of these recent examples. This study presents the identification and analytical characterization of two powdered 4F-MPH products that were obtained from an online vendor in 2015. Interestingly, the products appeared to have originated from two distinct batches given that one product consisted of (±)-threo-4F-MPH isomers whereas the second sample consisted of a mixture of (±)-threo and (±)-erythro 4F-MPH. Monoamine transporter studies using rat brain synaptosomes revealed that the biological activity of the 4F-MPH mixture resided with the (±)-threo and not the (±)-erythro isomers based on higher potencies determined for blockage of dopamine uptake (IC50 4F-MPHmixture =66nM vs. IC50 (±)-threo=61nM vs. IC50 (±)-erythro=8,528nM) and norepinephrine uptake (IC50 4F-MPHmixture =45nM vs. (±)-threo=31nM vs. IC50 (±)-erythro=3,779nM). In comparison, MPH was three times less potent than (±)-threo-4F-MPH at the dopamine transporter (IC50 =131nM) and around 2.5 times less potent at the norepinephrine transporter (IC50 =83nM). Both substances were catecholamine selective with IC50 values of 8,805nM and >10,000nM for (±)-threo-4F-MPH and MPH at the serotonin transporter. These findings suggest that the psychostimulant properties of (±)-threo-4F-MPH might be more potent in humans than MPH. Copyright © 2017 John Wiley & Sons, Ltd.